Disentangling gray matter atrophy and its neurotransmitter architecture in drug-naïve Parkinson’s disease: an atlas-based correlation analysis DOI

Huize Pang,

Xiaolu Li, Ziyang Yu

et al.

Cerebral Cortex, Journal Year: 2024, Volume and Issue: 34(10)

Published: Oct. 1, 2024

Parkinson's disease is characterized by multiple neurotransmitter systems beyond the traditional dopaminergic pathway, yet their influence on volumetric alterations not well comprehended. We included 72 de novo, drug-naïve patients and 61 healthy controls. Voxel-wise gray matter volume was evaluated between controls, as among subgroups categorized clinical manifestations. The Juspace toolbox utilized to explore spatial relationship atrophy distribution. exhibited widespread GM in cerebral cerebellar regions, with correlations various receptors (FDR-P < 0.05). Cognitively impaired showed left middle temporal atrophy, which associated serotoninergic, dopaminergic, cholinergic, glutamatergic Postural gait disorder right precuneus, correlated gamma-aminobutyric acid, opioid Patients anxiety superior orbital frontal region; those depression lingual inferior occipital regions. Both conditions were linked serotoninergic regional a significant distribution of specific neurotransmitters, might provide insights into underlying pathophysiology manifestations develop targeted intervention strategies.

Language: Английский

A Multimodal Meta-Analytical Evidence of Functional and Structural Brain Abnormalities Across Alzheimer's Disease Spectrum DOI
Xinyue Tang, Zixuan Guo, Guanmao Chen

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102240 - 102240

Published: Feb. 22, 2024

Language: Английский

Citations

23
Unraveling neurotransmitter changes in de novo GBA-related and idiopathic Parkinson's disease DOI Creative Commons
Jingru Ren, Lei Yan, Hao Zhou

et al.

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 185, P. 106254 - 106254

Published: Aug. 7, 2023

Presently, neurotransmitter deficits in GBA-related Parkinson's disease (GBA-PD) and relationships with cognitive impairment are poorly understood. A better understanding of impairments GBA-PD - particularly the newly diagnosed drug-naïve phase may support developing targeted intervention strategies. We aimed to investigate patterns idiopathic PD (iPD) performance correlations.We recruited 189 patients for GBA sequencing. Voxel-wise gray matter volume (GMV) was evaluated a subgroup 17 GBA-PD, 100 iPD, 32 age- sex-matched healthy controls (HCs). The JuSpace toolbox covering various maps helped assess whether spatial GMV alterations or iPD (relative HCs) were associated specific systems.GBA-PD indicated widespread GM atrophy fronto-temporal-occipital region compared HCs. spatially correlated serotonergic, dopaminergic, acetylcholinergic pathway distributions (p < 0.05, false discovery rate corrected). Executive function language domains also strength colocalization circuits.Regional related de novo could provide new insights into pathophysiological processes, facilitating potential therapeutic targets management.

Language: Английский

Citations

16
Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson’s disease DOI Creative Commons
Ahmed Faraz Khan, Quadri Adewale, Sue‐Jin Lin

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 26, 2023

Abstract Parkinson’s disease involves multiple neurotransmitter systems beyond the classical dopaminergic circuit, but their influence on structural and functional alterations is not well understood. Here, we use patient-specific causal brain modeling to identify latent receptor-mediated mechanisms contributing progression. Combining spatial distribution of 15 receptors from post-mortem autoradiography with 6 neuroimaging-derived pathological factors, detect a diverse set influencing gray matter atrophy, activity dysregulation, microstructural degeneration, dendrite transporter loss. Inter-individual variability in receptor correlates symptom severity along two distinct axes, representing motor psychomotor symptoms large GABAergic glutamatergic contributions, cholinergically-dominant visuospatial, psychiatric memory dysfunction. Our work demonstrates that architecture helps explain multi-factorial re-organization, suggests distinct, co-existing processes underlie disease.

Language: Английский

Citations

15
Beyond the usual suspects: multi-factorial computational models in the search for neurodegenerative disease mechanisms DOI Creative Commons
Ahmed Faraz Khan, Yasser Iturria‐Medina

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 23, 2024

Language: Английский

Citations

4
Disparate and shared transcriptomic signatures associated with cortical atrophy in genetic behavioral variant frontotemporal degeneration DOI Creative Commons
Ting Shen, Jacob W. Vogel, Vivianna M. Van Deerlin

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 7, 2025

Cortical atrophy is a common manifestation in behavioral variant frontotemporal degeneration (bvFTD), exhibiting spatial heterogeneity across various genetic subgroups, which may be driven by distinct biological mechanisms. We employed an integrative imaging transcriptomics approach to identify both disparate and shared transcriptomic signatures associated with cortical thickness bvFTD C9orf72 repeat expansions or pathogenic variants GRN MAPT. Functional enrichment analyses were conducted on each gene list significantly thickness. Additionally, we mapped neurotransmitter receptor/transporter density maps the maps, uncover different correlation patterns for form. Furthermore, examined whether identified genes enriched pathology-related using previously linked TDP-43 positive neurons tau pathology. For form of bvFTD, sets them. The GRN-bvFTD involved system circadian entrainment. correlations between synaptic thinning, further confirmed critical role neurotransmission signaling shaping brain structure, especially group. observed significant overlap pathology C9orf72-bvFTD but not MAPT-bvFTD group providing specificity our associations. also displaying consistent directionality, those either negative showing same direction (positive negative) GRN-bvFTD. displayed more pronounced differences compared other two forms. that exhibited showed opposing directionality Overall, this several new regional vulnerability increased interpretation including pathologically-specific expression. These findings illuminated intricate molecular underpinnings contributing heterogeneous nature disease distribution backgrounds.

Language: Английский

Citations

0
Gray matter alterations and neurotransmitter system associations in hepatitis B virus-related cirrhosis: insights into neuropathogenesis and therapeutic targets DOI

Lubin Gou,

Junqiang Lei, Huiwen Ren

et al.

Neuroradiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Language: Английский

Citations

0
Cognitive impairment in neurodegenerative diseases: A trans-diagnostic approach using a lesion-symptom mapping analysis DOI

Ricardo Félix Morais,

Ricardo Flores Pires,

Tiago Jesus

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Differential involvement of neurotransmitter pathways in AD, bvFTD and MCI: Whole-brain MRI analysis DOI Creative Commons

Ricardo Félix Morais,

José Maria Sousa, Cemal Koba

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106897 - 106897

Published: April 1, 2025

Neurodegenerative diseases, including Alzheimer's disease (AD), mild cognitive impairment (MCI), and frontotemporal dementia (FTD), are a growing public health challenge, with incidence projected to triple in the coming decades. AD is associated memory impairment, bvFTD behavioral dysfunction, MCI as transitional stage between normal cognition dementia. While structural brain changes have been widely studied, role of neurotransmitter pathways remains underexplored. This study aims correlate gray matter atrophy AD, bvFTD, identify distinctive neurochemical impairments. We included 214 participants (89 CE, 74 51 MCI) from single-center cohort. MRI 3 T scanners was segmented via FreeSurfer. Neurotransmitter maps were sourced JuSpace. performed volumetric whole-brain correlation analyses evaluate relationships regional volumes (BRVs) pathways. Group differences assessed Kruskal-Wallis tests followed by post-hoc analyses. Volumetric analysis showed expected patterns each group. Correlation indicated distinct involvement: significant correlations dopamine D2 GABA A receptor distribution; had negative mu-opioid receptor; exhibited early serotonergic dysregulation. identified linked specific systems, showing unique profiles. In precuneus inferior parietal lobules aligns dopaminergic GABAergic receptors, potentially impacting executive functions. medial orbitofrontal temporal atrophy, possibly contributing symptoms. MCI, dysregulation involving SERT occurs before detectable atrophy.

Language: Английский

Citations

0
Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells DOI Creative Commons
Katarzyna Gaweda‐Walerych, Vanessa Aragona, Simona Lodato

et al.

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 16, 2025

Abstract Heterozygous mutations in GRN gene lead to insufficient levels of the progranulin (PGRN) protein, resulting frontotemporal dementia (FTD) with TAR DNA-binding protein 43 (TDP-43) inclusions, classified pathologically as lobar degeneration (FTLD-TDP). Homozygous are exceedingly rare and cause neuronal ceroid lipofuscinosis 11, a lysosomal storage disease onset young adulthood, or an FTD syndrome late-onset manifestations. In this review, we highlight broad spectrum clinical phenotypes associated PGRN deficiency, including primary progressive aphasia behavioral variant dementia. We explore these alongside relevant rodent vitro human models, ranging from induced pluripotent stem cell-derived neural progenitors, neurons, microglia, astrocytes genetically engineered heterotypic organoids containing both neurons astrocytes. summarize advantages limitations models recapitulating main FTLD- hallmarks, highlighting role non-cell-autonomous mechanisms formation TDP-43 pathology, neuroinflammation, neurodegeneration. Data obtained patients’ brain tissues biofluids, parallel single-cell transcriptomics, demonstrate complexity interactions among highly heterogeneous cellular clusters present brain, astrocytes, oligodendroglia, endothelial cells, pericytes. Emerging evidence has revealed that deficiency is cell cluster-specific, often conserved, genetic molecular central nervous system. focus on how distinct populations their dysfunctional crosstalk contribute neurodegeneration neuroinflammation FTD- . Specifically, characterize lipid droplet-accumulating microglia alterations myelin content dysfunction caused by deficiency. Additionally, consider deregulation glia-neuron communication affects exchange organelles such mitochondria, removal excess toxic products aggregates, PGRN-related

Language: Английский

Citations

0
Deciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing DOI Creative Commons
Cyril Pottier, Fahri Küçükali,

Matt Baker

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 25, 2025

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder only limited number risk loci identified. We report our comprehensive genome-wide association study as part International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe Australia, meta-analysis Dementia-seq cohort. confirm UNC13A strongest overall factor identify TNIP1 novel factor. In subgroup analyzes, we further significant specific to each three main pathological subtypes (A, B C), well enrichment distinct tissues, brain regions, subtypes, suggesting disease aetiologies subtypes. Rare variant analysis confirmed TBK1 identified C3AR1, SMG8, VIPR1, RBPJL, L3MBTL1 ANO9, subtype-specific genes, highlighting role innate adaptive immunity notch signaling pathway FTLD-TDP, potential diagnostic therapeutic implications.

Language: Английский

Citations

0